D-Day at FDA for B-MS/AZ diabetes drug dapagliflozin

Documents released ahead of a US regulatory panel meeting on Tuesday suggest Bristol-Myers Squibb/AstraZeneca's diabetes drug dapagliflozin will be in for a fairly rough ride over potential liver and cancer risks.

Papers have been published on the website of the US Food and Drug Administration ahead of a meeting of its Endocrinologic & Metabolic Drugs Advisory Committee on July 19 which will evaluate dapagliflozin, the first drug in the class of sodium-glucose co-transporter 2 (SGLT2) inhibitors. These drugs are designed to block glucose being absorbed into the bloodstream through the kidneys, allowing more sugar to be excreted with urine.

The FDA staffers are concerned about at least one case of dapagliflozin-induced liver injury. They also note that nine women, or 0.4% of those who took the drug, got breast cancer compared with one woman, (0.09%), of those in the control group. For bladder cancer, the rate was nine cases (0.3%) for those taking dapagliflozin compared with one case (0.05%) in the control group.

B-MS and AstraZeneca claim that when all types of cancer, not just breast and bladder, are considered, there is no increased risk with their drug. They also say that some of the cancers were diagnosed so soon after the start of the trials that a link to dapagliflozin cannot be made.

The FDA staffers also raised the issue of genital-urinary infections associated with dapagliflozin therapy and bone safety concerns. They also claim the drug is not effective in patients with moderate to severe kidney impairment.

Other observers say the drug would be a useful addition to tackling diabetes, given that the mechanism of action of dapagliflozin is independent of insulin, making it potentially easy to combine SGLT2 inhibitors with other diabetes drugs, not least B-MS/AstraZeneca's already-approved Onglyza (saxagliptin).

The dapagliflozin hearing comes in an important week for AstraZeneca which will also see an FDA panel decide whether it will recommend approval of the Anglo-Swedish drugmaker's anti-platelet drug Brilinta (ticagrelor).